This study proposes to characterize the lean phenotype in MCH knockout mice, and to ascertain the relative contributions of MCH and the two other peptides derived from the MCH gene, N-EI and N-GE. To determine the role of MCH in mediating the orexigenic or appetite inhibiting action of other neuropeptides the effect of appetite regulating peptides in MCH-/-will be assessed. In addition to examining the importance of mediating obesity in single gene models of rodent obesity, MCH-/-mice will be crossbred to leptin deficient (ob/ob) mice and leptin resistant A (agouti) mice. MCH-/- mice will be crossbred to mice with ablations NPY or orexin, other neuropeptides implicated in energy balance. Finally to determine the importance of MCH in mediating obesity in response to environmental agents, the ability of a high fat diet, MSG and GTG to cause obesity will be compared in wild type and MCH-/- animals.